Aging is an almost universal process within biological systems, one which leads to a decline in functional capacity, disease onset, and eventually death. There has been much interest in recent years to elucidate the molecular mec- nisms that underlie the aging process. Many theories have been proposed since the last century that aim to explain the causes of aging. There is no one theory that completely satisfies the phenotype of aging, but genetics and environm- tal factors play an important role in the etiology of age-related pathologies and the aging process. However, there is still much to be learned about the aging process which has been termed one of the last great frontiers in biology. De- graphic changes worldwide are leading to increased average life expectancies within our populations. These changes in population characteristics will impact upon the economies of the supporting society, with increasing healthcare and infrastructural costs arising from the prevalence of age-related pathologies and other physical disabilities associated with advancing years. Many researchers worldwide are working in the attempt to identify key cellular processes through which it might one day be possible to slow down the aging process and thus increase the health span of humans. Numerous research projects-from the cellular through to tissue, organ, and whole organism studies-are currently underway to investigate the mul- factorial aging process.

As the drug discovery process shifts more and more toward specifically targeting pathways and molecules, model systems continue to increase in importance, and the mouse, with its versatility, ease of use, and remarkable similarity to the human genome, has clearly risen to the forefront of animal model studies. In Mouse Models for Drug Discovery: Methods and Protocols, experts in the field present some background for those less familiar with mice as experimental model platforms as well as a collection of techniques involving general methods as well as specific disease topics such as type 1 and 2 diabetes, cardiovascular disease, arthritis, skin disorders, cancer, the use of behavioral models for depression and anxiety, neurodegenerative diseases, neuromuscular diseases, and infectious diseases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and easy-to-use, Mouse Models for Drug Discovery: Methods and Protocols will stimulate those not familiar with the power of the mouse and its potential for the drug discovery process, and it will encourage the development of new models and new ways to utilize existing models in order to further the use of this dynamic animal in this vital field."

This book is unique in covering a wide range of design and analysis issues in genetic studies of rare variants, taking advantage of collaboration of the editors with many experts in the field through large-scale international consortia including the UK10K Project, GO-T2D and T2D-GENES. Chapters provide details of state-of-the-art methodology for rare variant detection and calling, imputation and analysis in samples of unrelated individuals and families. The book also covers analytical issues associated with the study of rare variants, such as the impact of fine-scale population structure, and with combining information on rare variants across studies in a meta-analysis framework. Genetic association studies have in the last few years substantially enhanced our understanding of factors underlying traits of high medical importance, such as body mass index, lipid levels, blood pressure and many others. There is growing empirical evidence that low-frequency and rare variants play an important role in complex human phenotypes. This book covers multiple aspects of study design, analysis and interpretation for complex trait studies focusing on rare sequence variation. In many areas of genomic research, including complex trait association studies, technology is in danger of outstripping our capacity to analyse and interpret the vast amounts of data generated. The field of statistical genetics in the whole-genome sequencing era is still in its infancy, but powerful methods to analyse the aggregation of low-frequency and rare variants are now starting to emerge. The chapter Functional Annotation of Rare Genetic Variants is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book provides the most up-to-date review of the simian virus 40 (SV40) minichromosome as a model for the mammalian chromosome in studies of DNA replication. It focuses on disruption of DNA replication by anticancer drugs and DNA-damaging agents. There is a strong emphasis on the unique advantages of SV40 as an experimental system for the analysis of these classes of anticancer drug mechanisms. The new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication are covered in detail to aid readers in designing and interpreting similar experiments.
Key Features
* Presents unique advantages of SV40 as an experimental system for the study of classes of anticancer drugs
* Details new high-resolution gel electrophoresis methods for the analysis of SV40 DNA replication
* Provides details to help the reader design and interpret similar experiments

This book describes important developments and emerging trends in experimental and clinical cancer gene therapy. It reflects the tremendous advances made over recent years with respect to immunogenes, suicide genes and gene correction therapies, as well as in gene suppression and miRNA therapies. Many of the described strategies focus on the generation of more efficient and specific means of attack at known and novel cellular targets associated with tumor development and progression. The book also details parallel improvements in vector design, vector delivery, and therapeutic efficacy. It offers readers a stimulating, broad overview of advances in the field, linking experimental strategies to their clinical applications.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This book, written by one of the leaders in the field of the neurosciences, will give an explanation of the symptoms and eventual untimely suicide of one of literatures greatest authors; Virginia Woolf. The sources used are letters and statements from Woolf herself, the literature she wrote and comments, letters and any other documentation that referred to her mental state and her medical status. The author will use current insight into depression, the mental consequences of child abuse and drug interactions/effects to illustrate this case study. The book should appeal to researchers in the neurosciences, psychology and psychiatry as well as to a broader audience, mainly individuals who are interested in the (external and internal) forces that drove Woolf to write her material.

This volume is based on selected and updated papers from the symposium on "Basic Mechanisms of the EEG," which was held under the sponsor ship of the German EEG Society in Hamburg on September 28-29, 1990. The intention of this symposium was to relate recent experimental, clini cal, and neuropathological data on the basic mechanism that underlie the EEG. Although we know much about these mechanisms, there is still much more to be learned. The symposium was partly the continuation of an earlier symposium on "Origin of Cerebral Field Potentials" held in 1979 in Munster under the leadership of one of the present editors (E. -J. Speckmann) and H. Caspers. The present work combines new experimental and clinical results with state-of-the-art reports giving excellent general views. The first chapter presents a historical survey of the roots of current developments in neu rophysiology. It seems that in the near future we may decipher the EEG, which we have considered up to now somewhat as a cryptogram (chap ter 2). After chapter 3-a chapter concerned with more general points of the generation of cortical field potentials-chapters 4, 5, and 6 deal with several aspects and models of interactions and rhythms of cortical neurons. The role of glial cells in cortical electrical field generation is considered in chapter 7. Chapter 8 emphasizes the significance of brain metabolism."

This special issue of the Advances in Experimental Medicine and Biology presents much of the research described at the recent 2nd International Tissue Engineering Conference held in Crete in May 2005. The conference brought together over 150 researchers from around the world to examine the emerging and most advanced aspects of their particular field. The chapters reflect a diverse group of authors, including both clinicians and academicians.

This book, an international collaborative effort in the area of molecular respiratory research, showcases a broad range of multidisciplinary approaches to unravel and analyze the underlying mechanisms of a spectrum of respiratory ailments. It discusses immunological and genetic respiratory disorders, cancer, respiratory allergies and cough, sleep disordered breathing and many others. Exciting new results and up-to-date critical overviews of widely debated topics pertaining to respiratory disorders are presented. The contributions provide evidence for the growing interest of the international community of researchers in the field of respiration. The book incorporates modern molecular approaches to diagnostic and treatment solutions, underscoring the need for rational, evidence-based treatment methods. Combining cutting edge basic and clinical research with expert knowledge and experience this book is essential reading for medical students, research scientists and practicing specialists in pulmonology, immunology and allergology.

Organ regeneration, once unknown in adult mammals, is at the threshold of maturity as a clinical method for restoration of organ function in humans. Several laboratories around the world are engaged in the development of new tools such as stem cells and biologically active scaffolds. Others are taking fresh looks at well-known clinical problems of replacement of a large variety of organs: Bone, skin, the spinal cord, peripheral nerves, articular cartilage, the conjunctiva, heart valves and urologic organs. Still other investigators are working out the mechanistic pathways of regeneration and the theoretical implications of growing back organs in an adult. The time has come to present a collection of these efforts from leading practitioners in the field of organ regeneration.

The reader will soon find that this is more than a "how-to-do-it" book. It describes a philosophical approach to the use of statistics in the analysis of clinical trials. I have come gradually to the position described here, but I have not come that way alone. This approach is heavily influenced by my reading the papers of R.A. Fisher, F.S. Anscombe, F. Mosteller, and J. Neyman. But the most important influences have been those of my medical colleagues, who had important real-life medical questions that needed to be answered. Statistical methods depend on abstract mathematical theorems and often complicated algorithms on the computer. But these are only a means to an end, because in the end the statistical techniques we apply to clinical studies have to provide useful answers. When I was studying martingales and symbolic logic in graduate school, my wife, Fran, had to be left out of the intellectual excitement. But, as she looked on, she kept asking me how is this knowledge useful. That question, what can you do with this? haunted my studies. When I began working in bio statistics, she continued asking me where it was all going, and I had to explain what I was doing in terms of the practical problems that were being ad dressed."

In recent years, there have been major advances in the concepts and methodologies used in the study of retinal development at both cellular and molecular levels. These advanced methodologies have allowed and will continue to allow researchers to gain new insights into the molecular mechanisms underlying retinal development. In Retinal Development: Methods and Protocols, expert researchers in the field detail many of the protocols used for a wide range of experiments. These include protocols and techniques for manipulating gene expression in vivo, tracing cell fates with modernized classic blastomere manipulation in Xenopus and with Cre-based technique in mouse and in zebrafish, retinal regeneration and stem cell-based replacement, and ERG (function) recording and non-invasive imaging. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Retinal Development: Methods and Protocols provides methodologies crucial to the success of increasingly more complex and often challenging investigations in the fields of retinal development and other biological and biomedical research.

The discovery of uniform latex particles by polymer chemists of the Dow Chemical Company nearly 50 years ago opened up new exciting fields for scientists and physicians and established many new biomedical applications. Many in vitro diagnostic tests such as the latex agglutination tests, analytical cell and phagocytosis tests have since become rou tine. They were all developed on the basis of small particles bound to biological active molecules and fluorescent and radioactive markers. Further developments are ongoing, with the focus now shifted to applications of polymer particles in the controlled and di rected transport of drugs in living systems. Four important factors make microspheres interesting for in vivo applications: First, biocompatible polymer particles can be used to transport known amounts of drug and re lease them in a controlled fashion. Second, particles can be made of materials which bio degrade in living organisms without doing any harm. Third, particles with modified surfaces are able to avoid rapid capture by the reticuloendothelial system and therefore en hance their blood circulation time. Fourth, combining particles with specific molecules may allow organ-directed targeting."

Dr. Gordon Meiklejohn was a world renowned physician, and Chairman of the Department of Medicine at the University of Colorado. He is best known for being a catalyst in researching, diagnosing, and inoculating for the flu virus, and was instrumental in the eradication of Smallpox.Dr. Meiklejohn was the son of Alexander Meiklejohn. He excelled in academics and sports, especially ice hockey, and was twice invited to participate on the U.S. Olympic Hockey teams.

The discovery of microRNAs and its role as gene expression regulators in human carcinogenesis represents one of the most important scientific achievements of the last decade. More recently, other non-coding RNAs have been discovered and its implications in cancer are emerging as well, suggesting a broader than anticipated involvement of the non-coding genome in cancer. Moreover, completely new and unexpected functions for microRNAs are being revealed, leading to the identification of new anticancer molecular targets. This book represents a comprehensive guide on non-coding RNAs and cancer, spanning from its role as cancer biomarkers, to providing the most useful bioinformatic tools, to presenting some of the most relevant discoveries, which indicates how these fascinating molecules act as fine orchestrators of cancer biology.

In this book, research and development trends of physics, engineering, mathematics and computer sciences in biomedical engineering are presented. Contributions from industry, clinics, universities and research labs with foci on medical imaging (CT, MRT, US, PET, SPECT etc.), medical image processing (segmentation, registration, visualization etc.), computer-assisted surgery (medical robotics, navigation), biomechanics (motion analysis, accident research, computer in sports, ergonomics etc.), biomedical optics (OCT, soft-tissue optics, optical monitoring etc.) and laser medicine (tissue ablation, gas analytics, topometry etc.) give insight to recent engineering, clinical and mathematical studies.

Medical electronics, or more specifically the instrumentation used in physiological measurement, has changed significantly over the last few years. Developments in electronics technology have offered new and enhanced applications, especially in the areas of data recording and analysis and imaging technology. These changes have been accompanied by more stringent legislation on safety and liability. This book is designed to meet the needs of students on the growing number of courses, undergraduate and MSc. It is a concise and accessible introduction offering a broad overview that encompasses the various contributing disciplines.

Molecular diagnostic procedures have been described in a number of recent books and articles. However, these publications have not focused on virus detection, nor have they provided practical protocols for the newer molecular methods.
Written by the inventors or principal developers of these technologies, Molecular Methods for Virus Detection provides both reviews of individual methods and instructions for detecting virus nucleic acid sequences in clinical specimens. Each procedure includes quality assurance protocols that are often ignored by other methodology books. Molecular Methods for Virus Detection provides clinically relevant procedures for many of the newer diagnostic methodologies.
Key Features
* Provides state-of-the-art PCR methods for amplification, quantitation, " in situ" hybridization, and multiplex reactions
* Goes beyond PCR with protocols for 3SR, NASBA, LCR, SDA, and LAT
* Covers important virus detection methods such as "in situ" hybridization; Southern, dot, and slot blots; branched chain signal amplification; and chemiluminescence
* Includes quality control information crucial in research and clinical laboratories
* Most chapters are written by the inventors and principal developers of the methodologies
* Includes color plates, 77 figures, and 18 tables

This book describes, in fascinating detail, a variety of experiments sponsored by the U.S. government in which people were exposed to radiation without their knowledge. After reviewing hundreds of thousands of documents from the Atomic Energy Commission and other agencies, the Advisory Committee appointed by President Clinton in January 1994 found that nearly 4,000 human radiation experiments--most involving very low doses of radioactive tracers--were sponsored by the federal government between 1944-1974. This book documents these findings to provide a fascinating if not disturbing reminder of both the shocking standards for human experimentation and the shrouded practice of government secrecy in recent history. Carried out at the height of the Cold War, experiments included feeding radioactive cereal to teenagers at a school for the mentally retarded, irradiating the testicles of prison inmates, injecting plutonium into hospital patients, and intentional releases of radiation into the environment. The book places these experiments within their historical context, and a review of the relevant government policies and ethics standards at the time is included. The analysis is then applied to contemporary research on human subjects. The book concludes with a discussion of the Committee's key findings and a set of recommendations for changes in in institutional review boards, the interpretation of ethics rules and policies, the conduct of research involving military personnel, the oversight and accountability for ethical violations, compensation for research injuries, and balancing national securities interests with the rights of the public. This compelling volume will prove to be a landmark in the development of standards for human experimentation. Ethicists, public health professionals and those interested in the history of medicine and Cold War history will be intrigued by the findings in this volume.

Leland H. Hartwell Director, Fred Hutchinson Cancer Research Center, Nobel Laureate for Medicine, 2001 Yeast has proved to be the most useful single-celled organism for studying the fundamental aspects of cell biology. Resources are now available for yeast that greatly simplify and empower new investigations, like the presence of strains with each gene deleted, each protein tagged and databases on protein-protein interactions, gene regulation, and subcellular protein location. A powerful combination of genetics, cell biology, and biochemistry employed by thousands of yeast researchers has unraveled the complexities of numerous cellular processes from mitosis to secretion and even uncovered new insights into prion diseases and the role of prions in normal biology. These insights have proven, time and again, to foretell the roles of proteins and pathways in human cells. The collection of articles in this volume explores the use of yeast in pathway analysis and drug discovery. Yeast has, of course, supplied mankind's most ubiquitous drug for thousands of years. In one aspect, the role of yeast in drug discovery is much like the role of yeast in other areas of biology. Yeast offers the power of genetics and a repetoire of resources available in no other organism. Using yeast in the study of drug targets and metabolism can help to make a science of what has been largely an empirical activity. A science of drug discovery would permit rigorous answers to important questions.

Computational methodologies and modeling play a growing role for investigating mechanisms, and for the diagnosis and therapy of human diseases. This progress gave rise to computational medicine, an interdisciplinary field at the interface of computer science and medicine. The main focus of computational medicine lies in the development of data analysis methods and mathematical modeling as well as computational simulation techniques specifically addressing medical problems. In this book, we present a number of computational medicine topics at several scales: from molecules to cells, organs, and organisms. At the molecular level, tools for the analysis of genome variations as well as cloud computing resources for medical genetics are reviewed. Then, an analysis of gene expression data and the application to the characterization of microbial communities are highlighted. At the protein level, two types of analyses for mass spectrometry data are reviewed: labeled quantitative proteomics and lipidomics, followed by protein sequence analysis and a 3D structure and drug design chapter. Finally, three chapters on clinical applications focus on the integration of biomolecular and clinical data for cancer research, biomarker discovery, and network-based methods for computational diagnostics.

Diverse molecular, cellular, and environmental events must all come together to allow the successful formation of secondary cancers, metastases. The second edition of Metastasis Research Protocols, brings together updated versions of the seminal technique that were presented in the first edition and also includes new techniques that have recently been shown to be important in illuminating the processes underlying this important area of biology. Volume 2 presents techniques applicable at the level of living cells and tissues, and presents methodologies applicable to cell behaviour in vitro, in animal models and in mathematical constructs. The aim is the study of the interaction between cancer cells and their host/environment. The focus throughout is on the tools that have been shown to be helpful in unravelling the processes important in cancer metastasis. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Metastasis Research Protocols, Second Edition seeks to aid scientists in the further study of new methods in the area of metastasis research.

This thesis presents a method for reliably and robustly producing samples of amyloid- (A ) by capturing them at various stages of aggregation, as well as the results of subsequent imaging with various atomic force microscopy (AFM) methods, all of which add value to the data gathered by collecting information on the peptide's nanomechanical, elastic, thermal or spectroscopical properties. Amyloid- (A ) undergoes a hierarchy of aggregation following a structural transition, making it an ideal subject of study using scanning probe microscopy (SPM), dynamic light scattering (DLS) and other physical techniques. By imaging samples of A with Ultrasonic Force Microscopy, a detailed substructure to the morphology is revealed, which correlates well with the most advanced cryo-EM work. Early stage work in the area of thermal and spectroscopical AFM is also presented, and indicates the promise these techniques may hold for imaging sensitive and complex biological materials. This thesis demonstrates that physical techniques can be highly complementary when studying the aggregation of amyloid peptides, and allow the detection of subtle differences in their aggregation processes.